Are H. Aastveit

High apolipoprotein B, low apolipoprotein A-I, and improvement in the prediction of fatal myocardial infarction (AMORIS study): a prospective study

BACKGROUND Apolipoprotein B (apoB) and apolipoprotein A-I (apoA-I) are thought to be better predictors of acute myocardial infarction than total cholesterol and LDL-cholesterol. We investigated whether apoB and apoA-I are predictors of risk of fatal myocardial infarction. We also aimed to establish whether apoB and apoA-I add further information about risk of fatal myocardial infarction to that obtained with total cholesterol, triglycerides, and LDL-cholesterol. METHODS We recruited 175553 individuals mainly from screening programmes. We measured concentrations of apoB, apoA-I, total cholesterol, and triglycerides, and calculated apoB/apoA-I ratio and concentrations of LDL-cholesterol and HDL-cholesterol. The relation between death from acute myocardial infarction and initial values for apoB, apoA-I, and the other lipids was examined. FINDINGS Mean follow-up was 66.8 months (SD 41.3) for 98722 men and 64.4 months (41.4) for 76831 women. 864 men and 359 women had fatal myocardial infarction. In univariate analyses adjusted for age and in multivariate analyses adjusted for age, total cholesterol, and triglycerides, the values for apoB and apoB/apoA-I ratio were strongly and positively related to increased risk of fatal myocardial infarction in men and in women. ApoA-I was noted to be protective. In multivariate analysis, apoB was a stronger predictor of risk than LDL-cholesterol in both sexes. INTERPRETATION Although LDL-cholesterol and HDL-cholesterol are known risk factors, we suggest that apoB, apoB/apoA-I, and apoA-I should also be regarded as highly predictive in evaluation of cardiac risk. Although increased throughout the range of values of LDL-cholesterol, apoB and apoA-I might be of greatest value in diagnosis and treatment in men and women who have common lipid abnormalities, but have normal or low concentrations of LDL-cholesterol.

The apoB/apoA-I ratio is better than the cholesterol ratios to estimate the balance between plasma proatherogenic and antiatherogenic lipoproteins and to predict coronary risk

Abstract Background: The apolipoprotein B (apoB)/apoA-I ratio represents the balance of proatherogenic and antiatherogenic lipoproteins. The purpose of this study was to determine whether the apoB/apoA-I ratio was superior to any of the cholesterol ratios – total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C), low-density lipoprotein cholesterol (LDL-C)/HDL-C and non-HDL-C/HDL-C – in predicting the risk of coronary disease. Moreover, we examined whether any lipids, lipoproteins or cholesterol ratios add significant predictive information beyond that provided by the apoB/apoA-I ratio. Methods: Plasma lipids, lipoproteins, apoB, and apoA-I were measured in 69,030 men and 57,168 women above 40years of age. After a mean follow-up of 98months, 1183 men and 560 women had died from a myocardial infarction in this prospective apolipoprotein-related mortality risk (AMORIS) study. Results: High apoB and a high apoB/apoA-I ratio were strongly related to increased coronary risk, while high apoA-I was inversely related to risk. The apoB/apoA-I ratio was superior to any of the cholesterol ratios in predicting risk. This advantage was most pronounced in subjects with LDL-C levels <3.6mmol/l. Addition of lipids, lipoproteins or any cholesterol ratio to apoB/apoA-I in risk models did not further improve the strong predictive value of apoB/apoA-I. Conclusions: These results indicate that the apoB/apoA-I ratio is at present the best single lipoprotein-related variable to quantitate coronary risk. Given the additional advantages apolipoproteins possess – fasting samples are not required, apoB/apoA-I is a better index of the adequacy of statin therapy than LDL-C, and the measurement of apoB and apoA-I are standardized, whereas LDL-C and HDL-C are not – there would appear to be considerable advantage to integrating apolipoproteins into clinical practice.

Uric acid and risk of myocardial infarction, stroke and congestive heart failure in 417 734 men and women in the Apolipoprotein MOrtality RISk study (AMORIS)

Objectives.  Few studies have simultaneously analysed the influence of elevated serum uric acid (UA) on acute myocardial infarction (AMI), ischaemic and haemorrhagic stroke (IS, HS) and congestive heart failure (CHF) in large healthy populations. We, here, examine UA as a risk factor for AMI, stroke and CHF by age and gender in the Apolipoprotein MOrtality RISk (AMORIS) Study.

Lipids, myocardial infarction and ischaemic stroke in patients with rheumatoid arthritis in the Apolipoprotein-related Mortality RISk (AMORIS) Study

Objectives To examine the rates of acute myocardial infarction (AMI) and ischaemic stroke (IS) and to examine the predictive value of total cholesterol (TC) and triglycerides (TG) for AMI and IS in patients with rheumatoid arthritis (RA) and people without RA. Methods In the Apolipoprotein MOrtality RISk (AMORIS) Study 480 406 people (including 1779 with RA, of whom 214 had an AMI and 165 an IS) were followed for 11.8 (range 7–17) years. Cox regression analysis was used to calculate HR per SD increase in TC or TG with 95% CI. All values were adjusted for age, diabetes and hypertension. Results The levels of TC and TG were significantly lower in patients with RA than in people without RA. Despite this, the rate of AMI and IS per 1000 years was at least 1.6 times higher in RA than non-RA. TC was nearly significantly predictive for AMI (HR/SD 1.13 (95% CI 0.99 to 1.29), p=0.07) and significantly predictive for future IS in RA (HR/SD 1.20 (95% CI 1.03 to 1.40), p=0.02). TG had no relationship to development of AMI (1.07, 0.94 to 1.21, p=0.29), but was weakly related to IS (1.13, 0.99 to 1.27, p=0.06). In contrast, both TC and TG were significant predictors of AMI and IS in people without RA. Conclusions Patients with RA had 1.6 times higher rate of AMI and IS than people without RA. TC and TG were significant predictors of AMI and IS in people without RA, whereas the predictive value in RA was not consistent.

Stroke mortality and the apoB/apoA‐I ratio: results of the AMORIS prospective study

Objectives.  LDL cholesterol is a well‐established risk factor for myocardial infarction, but not for stroke. The main objective of the present study was to determine if the risk of stroke is related to the balance between the proatherogenic apoB lipoprotein particles and the antiatherogenic apoA‐I particles as is the case for myocardial infarction.

Errors that result from using the TC/HDL C ratio rather than the apoB/apoA-I ratio to identify the lipoprotein-related risk of vascular disease.

The objective of this analysis was to demonstrate the frequency and extent of error that results from using the TC/HDL C ratio rather than the apoB/apoA‐I ratio to estimate the lipoprotein‐related risk of vascular disease within 94 667 men and 75 675 women in the Apoprotein‐related Mortality Risk (AMORIS) cohort. The odds ratio (OR) for the risk of fatal myocardial infarction was determined for 1 SD change in the apoB/apoA‐I ratio and all the conventional cholesterol ratios – TC/HDL C ratio, LDL C/HDL C ratio, non‐HDL C/HDL C ratio. In both men and women, the apoB/apoA‐I ratio was significantly greater than any of the cholesterol ratios, which, in fact, differed little. Therefore, the apoB/apoA‐I ratio was taken as the most accurate index of the lipoprotein‐related risk of vascular disease. Using Receiver Operating Characteristic analysis, it was demonstrated that the diagnostic accuracy of the apoB/apoA‐I ratio was significantly greater than any cholesterol ratio in those with an LDL cholesterol <3.6 mmol L−1 compared to those with an LDL cholesterol >3.6 mmol L−1. Indeed, the difference between the apoB/apoA‐I OR compared with the TC/HDL C OR progressively widened as risk increased. This suggests that the advantage of the apoB/apoA‐I ratio is greatest in the population at highest risk. The distribution of subjects by quintiles showed in both genders that whilst agreement was greatest at the extremes, even at these points there was substantial discordance between the TC/HDL C and the apoB/apoA‐I ratios. Within the middle of the distribution, less than 50% of the values were concordant. Finally, when comparing the ORs, the TC/HDL C ratio underestimated risk in 69.4% of male subjects and overestimated risk in 26.1% of male subjects, whereas in the female subjects, the TC/HDL C ratio underestimated risk in 84.9% of the subjects and overestimated risk in 12.0%. Thus, using the conventional cholesterol ratios rather than the apoB/apoA‐I ratio results in frequent and substantial error in the estimation of the lipoprotein‐related risk of vascular disease.

Relationships between lipoprotein components and risk of myocardial infarction: age, gender and short versus longer follow-up periods in the Apolipoprotein MOrtality RISk study (AMORIS).

Objectives.  Examine and compare lipoprotein components associated with fatal and nonfatal acute myocardial infarction (AMI) by time period in the Apolipoprotein MOrtality RISk (AMORIS) Study.

Transcriptional Response of Enterococcus faecalis V583 to Erythromycin

ABSTRACT A transcriptional profile of Enterococcus faecalis V583 (V583) treated with erythromycin is presented. This is the first study describing a complete transcriptional profile of Enterococcus. E. faecalis is a common and nonvirulent bacterium in many natural environments, but also an important cause of nosocomial infections. We have used a genome-wide microarray based on the genome sequence of V583 to study gene expression in cells exposed to erythromycin. V583 is resistant to relatively high concentrations of erythromycin, but growth is retarded by the treatment. The effect of erythromycin treatment on V583 was studied by a time course experiment; samples were extracted at five time points over a period of 90 min. A drastic change in gene transcription was seen with the erythromycin-treated cells compared to the untreated cells. Altogether, 260 genes were down-regulated at one or more time points, while 340 genes were up-regulated. Genes encoding hypothetical proteins and genes encoding transport and binding proteins were the two most dominating groups of differentially expressed genes. The gene encoding ermB (EFA0007) was expressed, but not differentially, which indicated that other genes are important for the survival and growth maintenance of V583 treated with erythromycin. One of these genes is a putative MsrC-like protein, which was up-regulated at all time points studied. Other specific genes that were found to be up-regulated were genes encoding ABC transporters and two-component regulatory systems, and these may be genes that are important for the specific response of V583 to erythromycin.

Relationships between lipoprotein components and risk of ischaemic and haemorrhagic stroke in the Apolipoprotein MOrtality RISk study (AMORIS).

Objectives.  To compare lipoprotein components associated with ischaemic and haemorrhagic stroke by age and gender in the Apolipoprotein MOrtality RISk (AMORIS) Study (n = 148 600).

ANOVA Interactions Interpreted by Partial Least Squares Regression

SUMMARY The relatively new partial least squares (PLS) regression method is used to relate yearly differences in straw length of 15 barley genotypes to climatic variations over 9 years. After main effects of genotypes and years were removed by conventional two-way ANOVA, the residual table of genotype x year interactions was related to a table of rainfall, temperature, and global radiation at different stages throughout the growth season, over the 9 years. In contrast to ANOVA interaction analysis based on principal component analysis, the related PLS regression method gave a direct, parsimonious linear modelling of the systematic relationships between the two tables in one single estimation procedure. Two main factors were found. The first one related warm, dry weather during the ear emergence to higher straw lengths in 6-row barleys than in 2-row barleys. The second factor related climatic differences between the first and last part of the growing season to straw length variations in certain related 2-row barley genotypes.